In-vitro diagnostic analysis method and system

ABSTRACT

A method and system for automatic in-vitro diagnostic analysis are described. The method comprises adding a first reagent type and a second reagent type to a first test liquid during a first and second cycle times respectively. The addition of the first reagent type to the first test liquid comprises parallel addition of a second reagent type to a second test liquid during the first cycle time. The addition of the second reagent type to the first test liquid comprises parallel addition of a first reagent type to a third test liquid during the second cycle time, respectively.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to EP 14171899.9, filed Jun. 11, 2014,which is hereby incorporated by reference.

BACKGROUND

The present disclosure generally relates to a method and to a system forin-vitro diagnostic analysis involving pipetting of reagents.

In analytical laboratories, in particular in-vitro diagnosticlaboratories, a multitude of analyses on biological samples are executedin order to determine physiological and biochemical states of patients,which can be indicative of a disease, nutrition habits, drugeffectiveness, organ function and the like.

Sample processing throughput, i.e., the number of biological samplesanalyzed per hour, as well as the number of different tests that can becarried out, are generally important. For laboratories handlingthousands of samples each day, a small delay for each individual samplemakes a substantial difference in terms of overall laboratoryefficiency.

In order to meet this demand, optimal hardware design and efficientworkflow planning are required when developing an automated system forin-vitro diagnostics. In particular, an automated system for in-vitrodiagnostic analysis may be required to execute a large number ofscheduled process operations, which are repeated at intervals calledcycle times and it is important that the cycle times at parity ofprocess operations be as short as possible in order to maximizethroughput. Also, it is frequent that different tests require differenttest conditions, for example, different reaction times, different typesof reagents, different volumes, different detection times, and the like.Thus, the system should be also able to dynamically adapt the scheduledworkflow due to the various test requirements and variable sequence oftest orders and be able to respond quickly to anomalies, errors due tounexpected events, and the like.

Therefore, this is a need for an in-vitro diagnostic analysis system andmethod that achieves higher processing throughput and workflowefficiency by a programmed control of functional units operatingsynergistically in parallel on different samples across different cycletimes while enabling a time-saving anticipation of subsequent workflowoperations.

SUMMARY

According to the present disclosure, a system and an automatic in-vitrodiagnostic analysis method are presented. The method can comprisesadding a first reagent type to a first test liquid during a first cycletime. The addition of the first reagent type to the first test liquidcan comprise parallel addition of a second reagent type to a second testliquid during the first cycle time. The method can also comprise addinga second reagent type to the first test liquid during a second cycletime. The addition of the second reagent type to the first test liquidcan comprise parallel addition of a first reagent type to a third testliquid during the second cycle time.

Accordingly, it is a feature of the embodiments of the presentdisclosure to provide for an in-vitro diagnostic analysis system andmethod that achieves higher processing throughput and workflowefficiency by a programmed control of functional units operatingsynergistically in parallel on different samples across different cycletimes while enabling a time-saving anticipation of subsequent workflowoperations. Other features of the embodiments of the present disclosurewill be apparent in light of the description of the disclosure embodiedherein.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The following detailed description of specific embodiments of thepresent disclosure can be best understood when read in conjunction withthe following drawings, where like structure is indicated with likereference numerals and in which:

FIG. 1 illustrates a partial top view of a system for in vitrodiagnostics according to an embodiment of the present disclosure.

FIG. 2 illustrates a variant of the system of FIG. 1 according to anembodiment of the present disclosure.

FIG. 3A illustrates a partial top view of a vessel processing areaaccording to the embodiment of FIG. 2 according to an embodiment of thepresent disclosure.

FIG. 3B illustrates the same partial top of view of FIG. 3A except forthe position of a vessel gripper according to an embodiment of thepresent disclosure.

FIG. 4 illustrates some units of the system of FIG. 2 in greater detailaccording to an embodiment of the present disclosure.

FIG. 5 illustrates some units of the system of FIG. 1 in greater detailaccording to an embodiment of the present disclosure.

FIG. 6A illustrates shows a method of operation of the system of FIG. 2,which also applies to the system of FIG. 1 according to an embodiment ofthe present disclosure.

FIG. 6B illustrates a magnification of a detail of FIG. 6A according toan embodiment of the present disclosure.

DETAILED DESCRIPTION

In the following detailed description of the embodiments, reference ismade to the accompanying drawings that form a part hereof, and in whichare shown by way of illustration, and not by way of limitation, specificembodiments in which the disclosure may be practiced. It is to beunderstood that other embodiments may be utilized and that logical,mechanical and electrical changes may be made without departing from thespirit and scope of the present disclosure.

A “system for in-vitro diagnostics” can be an analytical apparatus, i.e.a laboratory automated instrument dedicated to the analysis of testliquids for in vitro diagnostics. Examples of such analyticalapparatuses can be clinical chemistry analyzers, coagulation analyzers,immunochemistry analyzers, hematology analyzers, urine analyzers andnucleic acid analyzers that can be used for the qualitative and/orquantitative detection of analytes present in the test liquids, todetect the result of chemical or biological reactions and/or to monitorthe progress of chemical or biological reactions. The analyticalapparatus can comprise functional units for pipetting and/or mixing ofsamples and/or reagents. The analytical apparatus may comprise a reagentholding unit for holding reagents to perform the analysis. Reagents maybe arranged, for example, in the form of containers or cassettescontaining individual reagents, or group of reagents, and placed inappropriate receptacles or positions within a storage compartment orconveyor. It may comprise a consumable feeding unit, for example, forfeeding reaction vessels.

The analytical apparatus can further comprise one or more mixing units,comprising, for example, a shaker to shake a vessel containing a testliquid, or a mixing paddle to mix liquids in a vessel or reagentcontainer. The analytical apparatus can further comprise a detectionsystem and can follow a workflow, for example, execute a number ofprocessing steps, which can be optimized for certain types of analysissuch as, for example, clinical chemistry, immunochemistry, coagulation,hematology, and the like.

The analytical apparatus may have different configurations according tothe need and/or according to the desired laboratory workflow. Additionalconfigurations may be obtained by coupling a plurality of apparatusestogether and/or adding modules. A “module” can be a work cell, typicallysmaller in size and weight than an entire analytical apparatus, whichcan have an auxiliary function to the analytical function of ananalytical apparatus and can work only together with an analyticalapparatus. A module can be configured to cooperate with one or moreanalytical apparatuses for carrying out dedicated tasks of a sampleprocessing workflow, which can occur for example before or afteranalysis of the sample, e.g. by performing one or more pre-analyticaland/or post-analytical steps. Examples of the pre-analytical and/orpost-analytical steps can be loading and/or unloading and/ortransporting and/or storing sample tubes or racks comprising sampletubes, loading and/or unloading and/or transporting and/or storingreagent containers or cassettes, loading and/or unloading and/ortransporting and/or storing and/or washing reaction vessels, e.g.cuvettes, loading and/or unloading and/or transporting and/or storingpipette tips or tip racks, reading and/or writing information bearinglabels, e.g. barcodes or RFID tags, washing pipette tips or needles orreaction vessels, e.g. cuvettes, mixing paddles, mixing of samples withother liquid, e.g. reagents, solvents, diluents, buffers, decapping,recapping, pipetting, aliquoting, centrifuging, and so on. An example ofsuch a module can be a sample loading and/or unloading unit forloading/unloading sample tubes.

According to some embodiments, the system can comprise a vesselprocessing area comprising at least one static vessel holder and atleast one movable vessel workstation that can comprise a vessel gripper.

The term “vessel” can be herein used to indicate a container comprisinga body and an inner space to receive liquids, e.g. to enable a reactionbetween one or more samples and one or more reagents and/or to enableanalyis of a test liquid contained therein. According to someembodiments, the vessel can be a cuvette, i.e. a container that can, atleast, in part, be optically transparent and shaped to allow thephotometric measurement, such as, for example, the measurement ofchanges in optical transmission, such as absorbance and scattering, of atest liquid contained therein. The cuvette may be used in theperformance of absorbance or scattering assays to detect the result of achemical or biological reaction or to monitor the progress of a chemicalor biological reaction, e.g. in a coagulation assay, agglutinationassay, turbidimetric assay. According to one embodiment, the cuvettebody can comprise side walls, a closed bottom and an upper opening forallowing liquids to be introduced in an inner space formed by the sidewalls and the closed bottom. According to one embodiment, the cuvettecan comprise at least one lip projecting outwards of the cuvette body inproximity of the upper opening. This lip may be convenient for grippingthe cuvette by the vessel gripper and/or for holding the cuvette in thestatic cuvette holder. The cuvette may have an inner volume in themilliliter or microliter range.

A “static vessel holder” can be a holding device comprising one or morestatic vessel holding positions such as, for example, in the form of arecess, cavity, frame, seat or the like. The term “static” can meanimmovable with respect to the rest of the system. The static vesselholder may be, for example, embodied as a fixed unit or block in avessel processing area. The unit or block may have one or more otherfunctions in addition to the holding function. The static vessel holdermay, for example, act as an incubation station to hold one or morevessels at a certain temperature for a certain time, sufficiently long,e.g., for a reaction between a test liquid and a reagent to be completedor to reach an acceptable degree of completion under the reactionconditions, and where the time can extend over more than one cycle time.The static vessel holder may also or, in alternative, act as a detectionstation to allow detection such as, for example, a photometricmeasurement, of a test liquid in a vessel. According to someembodiments, the static vessel holder can comprise at least one vesselholding position acting as an incubation position and/or at least onevessel holding position acting as a detection position, where the staticvessel holder may be divided in functional subunits on the same block ordifferent blocks, e.g., one subunit for incubation and one subunit fordetection. According to some embodiments, the at least one static vesselholder can comprise a plurality of linearly arranged vessel holdingpositions.

A “movable vessel workstation” can be a functional unit operativelycoupled to the static vessel holder and that can move with respect tothe static vessel holder. According to some embodiments, the at leastone vessel workstation can be translatable relative to the at least onestatic vessel holder to transfer vessels between different vesselholding positions of the at least one static vessel holder. The movablevessel work station can comprise a gripper for gripping vessels, e.g., avessel at a time, by which it is possible to place vessels into thevessel holding positions, remove vessels from the vessel holdingpositions and move vessels between vessel holding positions. The grippercan be embodied as a movable element of the movable vessel workstationcapable at least to be translatable in the vertical direction andcomprising jaws that can be opened and closed to grip or release avessel.

According to some embodiments, the movable vessel workstation cancomprise a shaking mechanism for shaking the vessel held by the gripperat least in part during transfer of the vessel between different vesselholding positions of the static vessel holder. According to anembodiment, the shaking mechanism can be an eccentric rotatablemechanism driven by a motor and coupled to the gripper for eccentricallyagitating the gripper and thereby a vessel can be held by the gripperresulting in a mixing of a liquid contained therein.

According to some embodiments, the vessel processing area can furthercomprise a vessel input station for feeding at least one vessel at atime to the at least one static vessel holder. The “vessel inputstation” can be a functional unit coupled to the at least one staticvessel holder for feeding new vessels to the at least one static vesselholder, e.g., for placing at least one new vessel at a time in at leastone vessel holding position of the at least one static vessel holder.

According to an embodiment, the vessel input station can be common to atleast two static vessel holders. The vessel input station may be coupledto a vessel distribution unit for feeding individual vessels to thevessel input station starting from a bulk supply. The vessel inputstation may be embodied as a workstation with a translatable and/orrotatable vessel gripper.

The system for in-vitro diagnostics can comprise at least one pipettehead comprising at least two pipetting devices movable in a space abovethe vessel processing area. A “pipetting device” can be a functionalunit of the system for pipetting test liquids and/or reagents comprisingat least one dispensing nozzle that may function also as an aspirationnozzle. The nozzle may be embodied as a reusable washable needle suchas, for example, a steel hollow needle, or as a pipette tip such as, forexample, a disposable pipette tip that can be regularly replaced, forexample before pipetting a different test liquid or reagent. At leasttwo pipetting devices can be mounted to a pipette head. According tosome embodiments, the pipette head can be moved by a head translationmechanism in one or two directions of travel in a plane, such as withguiding rails, and possibly in a third direction of travel orthogonal tothe plane, for example with a spindle drive. According to an embodiment,the pipetting head can be moved by a head translation mechanism in oneor two directions of travel in a horizontal plane and the pipettingdevices can be individually movable in the vertical direction of travelorthogonal to the plane. The term “mounted to” can herein be broadlyused to intend attached to, coupled to, or the like without referring toa particular position.

The system for in-vitro diagnostics can further comprise a controller. A“controller” can be a programmable logic controller running acomputer-readable program provided with instructions to performoperations in accordance with an operation plan. The controller can beprogrammed to control the at least one vessel workstation, the at leastone pipette head and the at least two pipetting devices for executing anumber of scheduled process operations. The scheduled process operationscan comprise the addition of a first reagent type and a second reagenttype to a first test liquid during a first and second cycle timerespectively, the addition of the first reagent type to the first testliquid comprising parallel addition of a second reagent type to a secondtest liquid during the first cycle time and the addition of the secondreagent type to the first test liquid comprising parallel addition ofthe first reagent type to a third test liquid during a second cycletime, respectively.

The operation plan may however further comprise other operations, suchas aspirating a test liquid, dispensing a test liquid, aspirating firstand second type reagents, washing aspiration/dispensing nozzles and/orreplacing disposable tips, and moving the pipetting head to anaspiration, a dispensing, an end or wash position. The operation planmay further comprise operations other than those associated withpipetting and moving of the pipetting devices. For example, theoperation plan may comprise one or more of the following: moving of testliquid containers, opening and/or closing of test liquid containers,piercing caps of test liquid containers, moving of vessels, mixing oftest liquids, and detecting the result of reactions. The controller maycomprise a scheduler for executing a sequence of steps within apredefined cycle time for a number of cycle times. The controller mayfurther determine the order of in vitro diagnostic tests according tothe assay type, urgency, and the like. The controller may furtherdynamically change the operation plan according to unusual occurringcircumstances or newly occurring test orders or events.

The term “test liquid” can herein be used to indicate either a sample ora mixture or solution of one or more samples and one or more reagents,object of a test, i.e. an in-vitro diagnostic analysis. The term“sample”, as used herein, can refer to a liquid material suitable forpipetting and being subjected to an in vitro diagnostic analysis, e.g.in order to detect one or more analytes of interest suspected to bepresent therein or to measure a physical parameter of the sample assuch, for example, pH, color, turbidity, viscosity, coagulation time,and the like. Examples of in vitro diagnostic tests can be clinicalchemistry assays, immunoassays, coagulation assays, hematology assays,nucleic acid testing, and the like. In some embodiments, the disclosedsystem can be suitable for coagulation in vitro diagnostic tests.

The sample can be derived from any biological source, such as aphysiological fluid, including, blood, saliva, ocular lens fluid,cerebral spinal fluid, sweat, urine, milk, ascites fluid, mucous,synovial fluid, peritoneal fluid, amniotic fluid, tissue, cells or thelike. The sample can be pretreated prior to use, such as preparingplasma from blood, diluting viscous fluids, lysis or the like; methodsof treatment can involve filtration, centrifugation, distillation,concentration, inactivation of interfering components, and the additionof reagents. A sample may be used directly as obtained from the sourceor following a pretreatment to modify the character of the sample, e.g.after being diluted with another solution or after having being mixedwith reagents e.g. to carry out one or more in vitro diagnostic tests.The term “sample” as used herein is therefore not only used for theoriginal sample but also relates to a sample which has already beenprocessed (pipetted, diluted, and mixed with reagents, enriched, havingbeen purified, having been amplified, and the like). According to anembodiment the sample is a citrate treated blood sample.

The term “reagent” can generally be used to indicate a liquid orsubstance required for treatment of a sample. Reagents may be anyliquid, e.g., a solvent or chemical solution, which can be mixed with asample and/or other reagent in order e.g., for a reaction to occur, orto enable detection. A reagent may be, for example, a diluting liquid,including water, may comprise an organic solvent or a detergent, or itmay be a buffer. A reagent in the more strict sense of the term may be aliquid solution containing a reactant, typically a compound or agentcapable e.g., of binding to or chemically transforming one or moreanalytes present in a sample. Examples of reactants can be enzymes,enzyme substrates, conjugated dyes, protein-binding molecules, nucleicacid binding molecules, antibodies, chelating agents, promoters,inhibitors, epitopes, antigens, and the like.

A “first reagent type” or “reagent of the first type” can be a reagentrequired at an earlier stage of a sample processing workflow for a firstreaction to occur and that can typically require a second reagent typeor reagent of the second type for a test to be completed. According toan embodiment, the first reagent type can be an incubation reagent,e.g., a reagent that is supposed to remain in contact with a sampleunder certain condition, e.g., a certain time and at a certaintemperature in order for the reaction to be completed or to reach anacceptable degree of completion. A single test may require one or morereagents of the first type, e.g., added sequentially at different timesof the reaction. Examples of reagents of the first type can be reagentsfor the determination of coagulation factors and other coagulationparameters, for example, activated partial thromboplastin time (APTT).

A “second reagent type” or “reagent of the second type” can be a reagentthat can be required at a later stage of a sample processing workflow bya test liquid which has already reacted with one or more reagents of thefirst type in order for a test to be completed, or can be a reagent thatcan per se be sufficient for a test to be completed without requiringthe addition of a reagent of the first type. A second reagent type canhave therefore the function of continuing the reaction of the firstreagent type or to stop the reaction of the first reagent type or toenable detection of the reaction of the sample with the first reagenttype. A second reagent type can be the only one or the last reagent tobe used in a test before or during detection. According to anembodiment, the second reagent type can be a time-trigger reagent, alsocalled a start reagent, i.e., a reagent that triggers a time measurementfrom the moment the second reagent type has been added to the testliquid. An example of time-trigger reagent can be a coagulation triggerreagent, for example, a salt solution such as a NaCl or CaCl2 solution.

A “cycle time” can be a recurring time window, typically having a fixedlength, during which a certain number of process operations, also called“jobs” or “work packages,” can be repeatedly carried out in a controlledsequence, called “cycle.” This may not necessarily mean however that allprocess operations which are carried out in a cycle can be repeated inanother cycle. Some process operations may repeatedly occur at everycycle, others may occur every two or more cycles. Also new processoperations may be introduced in a cycle, depending on newly added testorders and/or newly occurring circumstances, so that a cycle may bedynamically adapted. Also, there may be extraordinary cycles or changesduring a cycle in response to extraordinary conditions such as, forexample, in case of clogging of a pipetting device, in case of errorsdetected in pipetting or liquid level, in case of errors in handlingvessels, or the like. In general, only some process operations among allprocess operations occurring in a single cycle time can be dedicated tothe performance of one test. This can mean that in a single cycle,typically at least two tests can be carried out simultaneously, althoughtypically at different stages, i.e., different process operations can bededicated to different tests respectively in a single cycle time. Thus,a test can be typically completed over a plurality, e.g., two or more,cycle times, where different process operations for carrying out thetest may occur in different cycle times, and with possible timeintervals between cycle times, e.g., the time interval, during which atest liquid can be incubated.

When reference is made to a “first cycle time,” it can be intended anycycle time and when reference is made to a “second cycle time,” it canbe intended any cycle time coming after a first cycle time, where“after” can mean the next cycle time or two or more cycle times afterthe first cycle time.

The term “adding to a test liquid” or “addition to a test liquid” maynot necessarily be limited in time with respect to the presence of atest liquid. The addition of a first reagent type may occur before orafter the addition of a test liquid as long as the test liquid and thereagent or reagents come together as a result of the addition.

“Parallel adding” or “parallel addition” can mean that a first reagenttype and a second reagent type can be added simultaneously to tworespective test liquids. The term “simultaneously” however may notnecessarily mean starting and ending at the same time as this may dependon several factors, such as, for example, the volumes being added, whichmay be different. The term can thus include at least in part overlappingor one comprised in the other.

The term “dispensing” can refer to a pipetting operation, which cantypically be preceded by an aspiration operation of the liquid beingdispensed. Parallel dispensing may not necessarily imply parallelaspiration.

According to some embodiments, the controller can be programmed tocontrol the at least two pipetting devices and the at least one vesselworkstation to add the first reagent type into a vessel held by thestatic vessel holder and to add the second reagent type into a vesselheld by the gripper of the movable vessel workstation.

According to some embodiments, the gripper can be controlled to hold thevessel at a different height than the vessel held by the static vesselholder during the parallel addition of the first reagent type and thesecond reagent type.

According to some embodiments, the controller can be further programmedto control the vessel workstation to move the gripper to a dispensingposition for dispensing the second reagent type into the vessel held bythe gripper. The dispensing position can be defined based on theposition of the vessel held by the static vessel holder that within thesame cycle time can require the first reagent type and based on thedistance between respective pipetting devices on the same pipette head.

According to some embodiments, where the at least one static vesselholder can comprise at least one detection position, after addition ofthe second reagent type, the controller can further be programmed tocontrol the vessel workstation for transferring the vessel held by thegripper to the at least one detection position.

According to some embodiments, where the vessel workstation comprises ashaking mechanism, the controller can further be programmed to controlthe shaking mechanism for shaking the vessel held by the gripper atleast in part during transfer of the vessel between different positionsof the static vessel holder.

According to an embodiment, the system can comprise a static vesselholder and a sample/reagent pipette head comprising at least two reagentpipetting devices and at least one sample pipetting device.

According to an embodiment, the system can comprise at least two staticvessel holders, a reagent pipette head comprising at least three reagentpipetting devices and a sample pipette head comprising at least twosample pipetting devices.

A further system for in-vitro diagnostic analysis is also disclosed. Thecontroller can be programmed to control the at least one vesselworkstation, the at least one pipette head and the at least twopipetting devices for executing a number of scheduled process operationscomprising adding in parallel at least two reagents into at least tworespective vessels, at least one of the vessels being held by a staticvessel holder and at least one of the vessels being held by the gripperof a movable vessel workstation.

According to some embodiments, the controller can be programmed tocontrol the at least two pipetting devices to add an incubation reagentinto the vessel held by the static vessel holder and a time-triggerreagent into the vessel held by the gripper of the movable vesselworkstation. According to some embodiments, the controller can befurther programmed to control the movable vessel workstation for holdingthe vessel by the gripper at a different height than the vessel held bythe static vessel holder. According to some embodiments, the at leasttwo pipetting devices can be mounted to a single pipette head and thecontroller can be further programmed to control the movable vesselworkstation to move the vessel held by the gripper to a dispensingposition for dispensing the time-trigger reagent into the vessel. Thedispensing position can be defined based on the position of the vesselheld by the static vessel holder, which within the same cycle time canrequire an incubation reagent, and based on the distance between therespective pipetting devices on the single pipette head. According tosome embodiments, the method can further comprise shaking the vesselheld by the gripper while moving the vessel towards a detectionposition.

A further system for in-vitro diagnostic analysis is also disclosed. Thecontroller can be programmed to control the at least one vesselworkstation, the at least one pipette head and the at least twopipetting devices for executing a number of scheduled processoperations, comprising adding in parallel a time-trigger reagent and anincubation reagent to at least two test liquids into at least tworespective vessels.

According to some embodiments, the controller can be programmed tocontrol the at least two pipetting devices to add the incubation reagentinto a vessel held by a static vessel holder and to add the time-triggerreagent into a vessel held by the gripper of a vessel workstation.According to some embodiments, the controller can be further programmedto control the vessel workstation for holding the vessel by the gripperat a different height than the vessel held by the static vessel holder.According to some embodiments, the at least two pipetting devices can bemounted to a single pipette head and the controller can be furtherprogrammed to control the vessel workstation to move the vessel held bythe gripper to a dispensing position for dispensing the reaction-triggerreagent into the vessel. The dispensing position can be defined based onthe position of the vessel held by the static vessel holder, whichwithin the same cycle time can require an incubation reagent and basedon the distance between the respective pipetting devices on the singlepipette head. According to some embodiments, the method can furthercomprise shaking the vessel held by the gripper while moving the vesseltowards a detection position.

A further system for in-vitro diagnostic analysis is also disclosed. Thesystem can comprise a vessel processing area comprising two staticvessel holders and a common vessel input station for feeding vessels tothe static vessel holders. The vessel processing area can furthercomprise two movable vessel workstations, each comprising a vesselgripper and translatable relative to a respective static vessel holderto transfer vessels between different vessel holding positions of therespective static vessel holder. The system can further comprise areagent pipette head comprising at least three reagent pipetting devicesand a sample pipette head comprising at least two sample pipettingdevices. With this system, it can be possible to nearly double theoverall sample processing throughput (number of tests per hour) comparedto a system with one single static vessel holder and one sample/reagentpipette head without doubling the number of functional units. Thisconfiguration can be mostly optimized for high-throughput testing of twoof the most frequently ordered coagulation tests, like the Prothrombintime (PT) test and the activated partial thromboplastin time (APTT)test, where the PT test can require only a time-trigger reagent and theAPTT test can require an incubation reagent in a first stage and atime-trigger reagent in a second stage. An even higher throughput can beachieved if the tests are alternated in a test order sequence. The twostatic vessel holders may be advantageously dedicated to different testsrespectively.

An automatic in-vitro diagnostic analysis method is also disclosed. Themethod can comprise adding a first reagent type and a second reagenttype to a first test liquid during first and second cycle times,respectively. The addition of the first reagent type to the first testliquid can comprise parallel addition of a second reagent type to asecond test liquid during the first cycle time and the addition of thesecond reagent type to the first test liquid can comprise paralleladdition of a first reagent type to a third test liquid during thesecond cycle time, respectively.

According to some embodiments, the parallel addition of the firstreagent type and the second reagent type can be carried out with asingle pipette head. The single pipette head can comprise at least twopipetting devices. According to an embodiment, the at least twopipetting devices can be independently drivable in the verticaldirection.

According to some embodiments, the addition of the first reagent typecan comprise dispensing the first reagent type into a vessel held by astatic vessel holder and the addition of the second reagent type cancomprise dispensing the second reagent type into a vessel held by agripper of a movable vessel workstation.

According to an embodiment, the first reagent type can be an incubationreagent and the second reagent type can be a time-trigger reagent.

According to some embodiments, the method can comprise holding thevessel by the gripper and the vessel by the static vessel holder atdifferent heights respectively during parallel addition of the secondreagent type and the first reagent type respectively.

According to some embodiments, the method can comprise moving thegripper to a dispensing position for dispensing the second reagent typeinto the vessel held by the gripper. The dispensing position can bedefined based on the position of the vessel held by the static vesselholder that within the same cycle time requires the first reagent typeand based on the distance between respective pipetting devices on asingle pipette head.

According to some embodiments, the method can comprise shaking thevessel held by the gripper while moving the vessel towards a detectionposition.

A further automatic in-vitro diagnostic analysis method is described.The method can comprise dispensing in parallel with at least twopipetting devices at least two reagents into at least two respectivevessels, at least one of the vessels being held by a static vesselholder and at least one of the vessels being held by the gripper of avessel workstation.

According to some embodiments, the reagent dispensed into the vesselheld by the static vessel holder can be an incubation reagent and thereagent dispensed into the vessel held by the gripper of the vesselworkstation can be a time-trigger reagent. According to someembodiments, the method can further comprise holding the vessel by thegripper and the vessel by the static vessel holder at different heightsrespectively during parallel dispensing. According to some embodiments,the at least two pipetting devices can be mounted to a single pipettehead and the method can comprise moving the gripper to a dispensingposition for dispensing a reagent into the vessel held by the gripper.The dispensing position can be defined based on the position of thevessel held by the static vessel holder that within the same cycle timerequires a reagent and based on the distance between respectivepipetting devices on the single pipette head. According to someembodiments, the method can further comprise shaking the vessel held bythe gripper while moving the vessel towards a detection position.

A further automatic in-vitro diagnostic analysis method is described.The method can comprise adding in parallel with a single pipette headcomprising at least two pipetting devices a time-trigger reagent and anincubation reagent to at least two test liquids respectively. Accordingto some embodiments, the method can comprise adding the incubationreagent into a vessel held by a static vessel holder and adding thetime-trigger reagent into a vessel held by the gripper of a vesselworkstation. According to some embodiments, the method can furthercomprise holding the vessel by the gripper and the vessel by the staticvessel holder at different heights respectively during paralleldispensing. According to some embodiments, the method can comprisemoving the gripper to a dispensing position for dispensing thetime-trigger reagent into the vessel held by the gripper. The dispensingposition can be defined based on the position of the vessel held by thestatic vessel holder that within the same cycle time requires anincubation reagent, and based on the distance between respectivepipetting devices on the single pipette head. According to someembodiments, the method can further comprise shaking the vessel held bythe gripper while moving the vessel towards a detection position.

Referring initially to FIG. 1, FIG. 1 shows an example of system 100 forin-vitro diagnostic analysis such as, for example, a coagulationanalyzer. The system 100 can comprise a reagent holding unit 110 forholding reagents of the first type and of the second type to performdifferent coagulation tests. The reagent unit 110 can be embodied as aclosed and tempered storage compartment comprising access holes 111 fora pipetting nozzle to enter the compartment and withdraw an aliquot ofreagent. The system 100 can further comprise a sample loading/unloadingunit 120 for loading/unloading sample tube racks 121 comprising sampletubes. The system can further comprise a central vessel processing area130 (shown and explained in greater detail in relation to FIG. 5). Thevessel processing area 130 can comprise a linear static vessel holder140. The static vessel holder 140 can comprise a plurality of vesselholding positions 141. The vessel processing area 130 can furthercomprise a vessel input station 150 for feeding one vessel at a timeinto the static vessel holder 140. The vessel processing area 130 canfurther comprise a movable vessel workstation 160 linearly translatablewith respect to the static vessel holder 140 and coupled to the staticvessel holder 140 to transfer vessels between vessel holding positions141 of the static vessel holder 140.

The system 100 can further comprise a pipette head 170 comprising threepipetting devices (shown in FIG. 5). The pipette head 170 can betranslatably mounted on a horizontal arm 171 and the arm 171 can betranslatably coupled to an orthogonal guide rail 172. The pipette head170 can thus be movable in a space above the reagent unit 110, above thevessel processing area 130, and above the sample loading/unloading unit120. In addition, the pipetting devices can each be individuallytranslatable in a vertical direction such as to be able to access areagent container in the reagent unit 110 via holes 111, a sample tubein the sample loading/unloading unit 120, and a vessel in the vesselprocessing area 130. Using the same pipette head 170, test liquids canbe aspirated from sample tubes in the sample loading/unloading unit 120,reagents can be aspirated from reagent containers in the reagent unit110 and both test liquids and reagents can be dispensed into vessels inthe vessel processing area 130.

The system 100 can further comprise a controller 180 programmed tocontrol the execution of a number of scheduled process operationsincluding operation of the movable vessel workstation 160, of thepipette head 170 and of the pipetting devices (described more in detailin relation to FIGS. 5 and 6A).

FIG. 2 shows another system 100′, which is a variant of the system 100of FIG. 1. One difference between the system 100′ and the system 100 isthat the system 100′ can comprise a vessel processing area 130′, whichcompared to the vessel processing area 130 of the system 100 can furthercomprise a second linear static vessel holder 140′ and a second movablevessel workstation 160′ linearly translatable with respect to the secondstatic vessel holder 140′ and coupled to the static vessel holder 140′to transfer vessels between vessel holding positions 141′ of the secondstatic vessel holder 140′. Another difference between system 100′ andsystem 100 is that the system 100′ can comprise two pipette heads 170′,173 translatably mounted on two respective horizontal arms 171, 174. Asshown in FIG. 5, the first pipette head 170′ can comprise three reagentpipetting devices to aspirate reagents from the reagent unit 110 and todispense the reagents into vessels in the vessel processing area 130′.The second pipette head 173 can comprise two sample pipetting devices toaspirate test liquids from sample tubes in the sample loading/unloadingunit 120 and to dispense the test liquids into vessels in the vesselprocessing area 130′. The arms 171, 174 can be translatably coupled tothe same orthogonal guide rail 172. The two static vessel holders 140,140′ can be arranged parallel to each other and the vessel input station150, which can be identical to that of FIG. 1, can be symmetricallyarranged between the two static vessel holders to feed vessels to bothstatic vessel holders 140, 140′.

Another difference between system 100′ and system 100 is that the system100′ can further comprise a sample rack tray unit 122, which can becoupled as a module to the sample loading/unloading unit 120 forloading/unloading sample racks 121 into/from the sampleloading/unloading unit 120.

The system 100′ can further comprise a controller 180′ programmed tocontrol the execution of a number of scheduled process operationsincluding operation of the movable vessel workstations 160, 160′, of thepipette heads 170′, 173 and of the pipetting devices (described more indetail in relation to FIGS. 4 and 6A-6B).

FIGS. 3A-B are partial top views of the vessel processing area 130′(without pipetting devices) according to the embodiment of FIG. 2. FIGS.3A-B show from top, the arrangement of the two static vessel holders140, 140′ and the two respective movable vessel workstations 160, 160′with respect to each other and with respect to the vessel input station150. The first static vessel holder 140 and the second static vesselholder 140′ can be identical and arranged longitudinally parallel infront of each other. Their orientation can however be inverted, with thesecond static vessel holder 140′ rotated 180 degrees with respect to thefirst static vessel holder 140. The first and second static vesselholders 140, 140′ can be embodied as linear blocks, each comprising anarray of linearly arranged vessel holding positions 141, 141′respectively, part of which acting as incubation positions and part ofwhich acting as detection positions (as more in detail described withreference to FIG. 6A).

The vessel input station 150 can comprise a vessel gripper 151 and canbe arranged between the first static vessel holder 140 and the secondstatic vessel holder 140′ in a symmetrical manner so that upon rotationof the vessel gripper 151 180 degrees, a vessel 10 can be placed by thesame vessel gripper 151 either in a vessel holding position 141 of thefirst static vessel holder 140 or in a vessel holding position 141′ ofthe second static vessel holder 140′. The first movable vesselworkstation 160 and the second movable vessel workstation 160′ can beidentical to each other and arranged parallel to the respective staticvessel holders 140, 140′ on the outer sides of the respective staticvessel holders 140, 140′ and opposite to the central vessel inputstation 150. The first movable vessel workstation 160 can betranslatable with respect to the first static vessel holder 140 alongguide rail 162 and the second movable vessel workstation 160′ can betranslatable with respect to the second static vessel holder 140′ alongguide rail 162′ independently from the first movable work station 160.Thus, the first movable workstation 160 can be coupled to the firststatic vessel holder 140 to transfer vessels between vessel holdingpositions 141 of the first static vessel holder 140 and the secondmovable vessel workstation can be coupled to the second static vesselholder 140′ to transfer vessels between vessel holding positions 141′ ofthe second static vessel holder 140′.

The vessel input station 150 can be fixed in space with respect to thestatic vessel holders 140, 140′ so that only the vessel gripper 151 canbe translated vertically and can be rotated towards either of the staticvessel holders 140, 140′. Thus, the vessel input station 150 can place anew vessel 10 one at a time into only one input vessel holding position141 of the first static vessel holder 140 (FIG. 3B) and into only oneinput vessel holding position 141′ of the second static vessel holder140′ (FIG. 3A). These two input vessel holding positions 141, 141′ canbe detection positions dedicated to carry out a photometric blankmeasurement of each new vessel 10 placed in each static vessel holder140, 140′. The two respective movable vessel workstations 160, 160′ canthen transfer the vessels 10 from the two input vessel holding positions141, 141′ to any other vessel holding positions 141, 141′ according tothe scheduled process.

FIG. 4 shows in perspective the vessel processing area 130′ of FIG. 3B,with the addition of the two pipette heads 170′, 173 above the vesselprocessing area 130′. The vessel input station 150 can be embodied as avessel lift comprising a vessel gripper 151 that can be verticallytranslatable along a guide rail 152 and rotatable in a horizontal plane.The vessel gripper 151 can be coupled to a vessel distribution unit forfeeding individual vessels 10 to the gripper 151 at a lower positionwith respect to the guide rail 152. The vessel gripper 151 can thustransport one vessel 10 at a time from a vessel distribution unit at alower position to one of the vessel holding positions 141, 141′ of thestatic vessel holders 140, 140′ at an upper position.

The movable vessel workstations 160, 160′ can be linearly translatableparallel to the static vessel holder 140, 140′ respectively along guiderail 162, 162′ respectively. Also, the movable vessel workstation 160,160′ can each comprise a vessel gripper 161, 161′ respectively that canbe translatable in the vertical direction. Thus, the movable vesselworkstations 160, 160′ can independently move along the respectivestatic vessel holders 140, 140′ to bring the vessel grippers 161, 161′in correspondence to any of the vessel holding positions 141, 141′ andby vertically translating the vessel grippers 161, 161′, they can gripand pull a vessel 10 out of any vessel holding position 141, 141′ orplace a vessel 10 into any free vessel holding position 141, 141′ of therespective static vessel holder 140, 140′. Vessels 10 can thus readilybe transferred between different vessel holding positions 141, 141′ ofthe same static vessel holder 140, 140′ respectively, e.g., between anincubation position and a detection position, by the movable vesselworkstations 160, 160′.

The first pipette head 170′ can be a reagent pipette head comprisingthree reagent pipetting devices and, in particular, two reagentpipetting devices 175′ to pipette reagents of the second type and onereagent pipetting device 176′ to pipette reagents of the first type. Thereagent pipetting devices 175′ can each comprise a heating element 177′for heating a reagent of the second type to an optimal temperaturebetween reagent aspiration and reagent dispensing. The second pipettehead 173 can be a sample pipette head comprising two sample pipettingdevices 178′ to pipette samples from sample tubes, e.g., includingaspiration through a closure of a sample tube by piercing the closure.

The embodiment of FIG. 4 can achieve double sample processing throughputfor at least some tests compared to the embodiment of FIG. 5 withoutduplicating the number of functional units. At least one reagent needlecan be spared and one common vessel input station 150 can be used.

FIG. 5 shows in perspective the vessel processing area of the system 100of FIG. 1, comprising only one static vessel holder 140, only onemovable vessel workstation 160 and only one pipette head 170. The staticvessel holder 140, the movable vessel workstation 160 and the vesselinput station 150 as well as their functional relationship are the sameas in FIG. 4. The pipette head 170 can be a sample/reagent pipette headcomprising a first reagent pipetting device 175, a second reagentpipetting device 176 and a sample pipetting device 178. The firstreagent pipetting device 175 can pipette reagents of the first typewhereas the second reagent pipetting device 176 can pipette reagents ofthe second type. The second reagent pipetting device 176 can comprise aheating element 177 for heating a reagent of the second type to anoptimal temperature between reagent aspiration and reagent dispensing.The sample pipetting device 178 can pipette test liquids from sampletubes, e.g., including aspiration through a closure of a sample tube bypiercing the closure.

FIG. 6A and FIG. 6B (a magnification of a detail of FIG. 6A) showfurther details of part of the embodiment of FIG. 4 during operation,controlled by the controller 180′. Only one static vessel holder 140with the respective movable vessel workstation 160 and only one pipettehead 170′ are shown for clarity. The process of parallel addition of afirst reagent type and a second reagent type is shown. The same appliesalso to the embodiment of FIG. 5, except that a different pipette headcan be used.

The static vessel holder 140 can comprise a plurality of vessel holdingpositions 141 for holding a plurality of vessels 10. The static vesselholder 140 can comprise an incubation subunit 140A comprising aplurality of incubation positions 141A (in this example, twenty)embodied as cavities in an aluminum block complementary in shape to theshape of a vessel 10. The incubation subunit 140A can comprise atemperature regulating unit for regulating the temperature of vessels 10contained in the incubation positions 141A, e.g., for maintaining thevessels 10 at an optimal reaction temperature.

The static vessel holder 140 can further comprise a detection subunit140B comprising a plurality of detection positions 141B (in thisexample, thirteen). The detection subunit 140B can comprise aphotometric unit 142. The photometric unit 142 can comprise a lightsource 143 on one side of the detection positions 141B and an opticaldetector arranged inside the detection subunit 140B on the other side ofthe detection positions 141B. For each detection position 141B, therecan be an optical fiber 144 for guiding light from the light source 143through a vessel 10 placed in the detection position 141B and an opticaldetector placed on the opposite side of the detection position to detectlight passing through the vessel 10 in the detection position 141B.Thus, each detection position 141B can be arranged in an optical pathbetween an optical fiber 144 and an optical detector. The vessels 10 cantherefore conveniently be embodied as cuvettes comprising two paralleland transparent walls, which can be placed in the optical path. Light ofdifferent wavelengths may be guided through different optical fibers 144and/or light of different wavelengths may alternately be guided in thesame optical fibers 144. The light source 143 may be common to alloptical fibers 144 and can comprise a multi-wavelength light source,e.g., a broad spectrum light source or a plurality of light emittingelements with individual wavelengths or wavelength ranges.

One of the detection positions 141B′ can be a blank measurement positionfor taking a blank measurement of each new vessel 10. In addition, theblank measurement position 141B′ can be the input vessel holdingposition where one new vessel 10 at a time can be placed by the vesselgripper 151 of the vessel input station 150.

The static vessel holder 140 can further comprise a waste port 145embodied as a hole though the static vessel holder 140 located betweenthe incubation subunit 140A and the detection subunit 140B. The hole 145can lead to a vessel waste bin located underneath the static vesselholder 140 for disposing used vessels 10 by the vessel gripper 161.

With reference to all embodiments, part of an exemplary process is nowdescribed. The following process describes some of the processoperations that can occur in a cycle time. The vessel input station 150can place one new vessel 10 at a time into the input vessel holdingposition 141B′ of the static vessel holder 140 and/or into acorresponding input vessel holding position 141′ of the second staticvessel holder 140′, depending on whether an embodiment with one or twostatic vessel holders 140, 140′ is used. A photometric blank measurementof each new vessel 10 in each static vessel holder 140, 140′ can then befirst carried out. After taking a photometric blank measurement of thevessel 10, the respective movable vessel workstations 160, 160′ cantransfer the vessels 10 to a free incubation position 141A, 141′ of therespective static vessel holder 140, 140′.

With reference to FIG. 2, FIG. 4, FIGS. 6A-B, the sample pipette head173 can move to the sample loading/unloading unit 120 and aspirate twotest liquids from two sample tubes or two aliquots from the same sampletube with the two respective pipetting devices 178′. The sample pipettehead 173 can then move to the first static vessel holder 140 to dispensea test liquid into a vessel 10 in an incubation position 141A and to thesecond static vessel holder 140′ to dispense the other test liquid intoanother vessel 10 into an incubation position 141′ of the second staticvessel holder 140′ or into another vessel 10 into an another incubationposition 141A of the first static vessel holder 140. The reagent pipettehead 170′ can move to the reagent unit 110 and aspirate one reagent ofthe first type and two reagents of the second type with reagentpipetting devices 176′ and 175′ respectively.

The gripper 161 of the first movable vessel workstation 160 can grip avessel 10B from an incubation position 141A. The first movable vesselworkstation 160 can then move to a dispensing position for dispensingthe second reagent type into the vessel 10B held by the gripper 161. Thedispensing position as shown in FIGS. 6A-B can be defined based on theposition of a vessel 10A held in an incubation position 141A of thestatic vessel holder 140 that within the same cycle time requires thefirst reagent type, and based on the distance between respectivereagents pipetting devices 175′, 176′ on the reagent pipette head 170′.

The reagent pipette head 170′ can move with respect to the first staticvessel holder 140 such that a reagent pipetting device 176′ containing areagent of the first type is positioned above the vessel 10A requiringthe reagent of the first type and the reagent pipetting device 175′containing the reagent of the second type is placed above the vessel 10Bheld by the vessel gripper 161 and requiring a reagent of the secondtype. The reagent pipetting devices 176′, 175′ can be then lowered atdifferent heights into respective vessels 10A, 10B for the paralleladdition of the first reagent type and the second reagent typerespectively. The reagent pipetting devices 175′, 176′ can then beraised and the vessel 10B held by the gripper 161 can be transported toa free detection position 141B of the detection subunit 140B fordetection, by linearly translating the movable vessel workstation 160.While moving the movable vessel workstation 160 between the dispensingposition and a detection position 141B, the gripper can shake the vessel10B for mixing the test liquid and the reagent of the second typecontained therein. By parallel addition of an incubation reagent and atime-trigger reagent with the same pipetting head and by synergisticcooperation of the movable vessel workstation, the use of functionalresources can be optimized and workflow efficiency can be increased withsignificant time savings, space savings and cost reduction. By holdingthe vessel 10B by the gripper 161 and pipetting a time-trigger reagentin the vessel 10B held by the gripper, the time between addition of thetime-trigger reagent and start of detection can be minimized. By shakingthe vessel 10B during transportation the time for mixing can also beminimized thus contributing to minimize the time between addition of thetime-trigger reagent and start of the detection.

After parallel addition of the a reagent of the first type and a reagentof the second type into two vessels 10A, 10B at the first static vesselholder 140, the reagent pipette head 170′ can move to the second staticvessel holder 140′ for dispensing the second reagent of the second typeinto a vessel 10 held by the vessel gripper 161′ of the second staticvessel holder 140′.

The vessel 10, 10A that has received a reagent of the first type canremain in incubation for one or more cycle times before receiving areagent of the second type in a subsequent cycle time.

In one embodiment, the first static vessel holder 140 can be dedicatedat least temporarily to a test type, e.g., to carry out APTT tests,whereas the second static vessel holder 140′ can be dedicated to adifferent test type, e.g., to carry out PT tests. Thus in a cycle,parallel addition of an incubation reagent and a time-trigger reagentcan take place at the first static vessel holder 140 into two respectivevessels 10A, 10B in performance of two APPT tests at different stagesrespectively, followed by addition of a time-trigger reagent into avessel 10 at the second static vessel holder 140′, such as into a vesselheld by the gripper 161′ of the second movable vessel workstation 160′,in performance of a PT test, the PT test requiring only a time-triggerreagent. The same procedure may be repeated in a subsequent cycle fordifferent test liquids and vessels 10 respectively. The system 100′ canbe thus programmed to perform high-throughput analysis of two of themost frequently used tests in coagulation analysis.

With reference to the embodiment of FIGS. 1 and 5, the process can besimilar, the difference being that there is one sample pipetting device178 and two reagent pipetting device 175, 176 for a reagent of the firsttype and second type respectively on the same sample/reagent pipettehead 170 and there is only one static vessel holder 140. The process ofparallel addition and transportation of the vessel 10B held by thegripper 161 can otherwise be the same.

Obviously modifications and variations of the disclosed embodiments arepossible in light of the above description. It is therefore to beunderstood, that within the scope of the appended claims, the presentdisclosure may be practiced otherwise than as specifically devised inthe above examples.

It is noted that terms like “preferably,” “commonly,” and “typically”are not utilized herein to limit the scope of the claimed embodiments orto imply that certain features are critical, essential, or evenimportant to the structure or function of the claimed embodiments.Rather, these terms are merely intended to highlight alternative oradditional features that may or may not be utilized in a particularembodiment of the present disclosure.

Having described the present disclosure in detail and by reference tospecific embodiments thereof, it will be apparent that modifications andvariations are possible without departing from the scope of thedisclosure defined in the appended claims. More specifically, althoughsome aspects of the present disclosure are identified herein aspreferred or particularly advantageous, it is contemplated that thepresent disclosure is not necessarily limited to these preferred aspectsof the disclosure.

We claim:
 1. An automatic in-vitro diagnostic analysis methodcomprising: adding a first reagent type to a first test liquid during afirst cycle time, wherein the addition of the first reagent type to thefirst test liquid comprising parallel addition of a second reagent typeto a second test liquid during the first cycle time; and adding thesecond reagent type to the first test liquid during a second cycle time,wherein the addition of the second reagent type to the first test liquidcomprising parallel addition of the first reagent type to a third testliquid during the second cycle time.
 2. The method according to claim 1,wherein the parallel addition of the first reagent type and the secondreagent type is carried out with a single pipette head.
 3. The methodaccording to claim 2, wherein the single pipette head comprising atleast two pipetting devices.
 4. The method according to claim 1, whereinthe first reagent type is an incubation reagent and the second reagenttype is a time-trigger reagent.
 5. The method according to claim 1,wherein the addition of the first reagent type comprises dispensing thefirst reagent type into a vessel held by a static vessel holder andwherein the addition of the second reagent type comprises dispensing thesecond reagent type into a vessel being held by a gripper of a movablevessel workstation.
 6. The method according to claim 5, furthercomprising, holding the vessel by the gripper and the vessel by thestatic vessel holder at different heights respectively during paralleladdition of the second reagent type and the first reagent typerespectively.
 7. The method according to claim 5, further comprising,moving the gripper to a dispensing position for dispensing the secondreagent type into the vessel held by the gripper, wherein the dispensingposition is defined based on the position of the vessel held by thestatic vessel holder that within the same cycle time requires the firstreagent type and based on the distance between respective pipettingdevices on a single pipette head.
 8. The method according to claim 5,further comprising, shaking the vessel held by the gripper while movingthe vessel towards a detection position.
 9. A system for in-vitrodiagnostic analysis, the system comprising: a vessel processing areacomprising at least one static vessel holder and at least one movablevessel workstation comprising a vessel gripper; at least one pipettehead comprising at least two pipetting devices movable in a space abovethe vessel processing area; and a controller programmed to control theat least one vessel workstation, the at least one pipette head and theat least two pipetting devices for executing a number of scheduledprocess operations comprising: the addition of a first reagent type to afirst test liquid during a first cycle time, the addition of a secondreagent type to the first test liquid during a second cycle time, theaddition of the first reagent type to the first test liquid comprisingparallel addition of a second reagent type to a second test liquidduring the first cycle time, and the addition of the second reagent typeto the first test liquid comprising parallel addition of the firstreagent type to a third test liquid during a second cycle time,respectively.
 10. The system according to claim 9, wherein thecontroller is programmed to control the at least two pipetting devicesand the at least one vessel workstation to add the first reagent typeinto a vessel held by the static vessel holder and to add the secondreagent type into a vessel held by the gripper of the movable vesselworkstation.
 11. The system according to claim 9, wherein the gripper iscontrolled to hold the vessel at a different height than the vessel heldby the static vessel holder during the parallel addition of the firstreagent type and the second reagent type.
 12. The system according toclaim 9, wherein the controller is further programmed to control thevessel workstation to move the gripper to a dispensing position fordispensing the second reagent type into the vessel held by the gripper.13. The system according to claim 12, wherein the dispensing position isdefined based on the position of the vessel held by the static vesselholder that within the same cycle time requires the first reagent typeand based on the distance between respective pipetting devices on thesame pipette head.
 14. The system according to claim 9, wherein thevessel processing area further comprises a vessel input station forfeeding at least one vessel at a time to the at least one static vesselholder.
 15. The system according to claim 9, wherein the at least onevessel workstation is translatable relative to the at least one staticvessel holder to transfer vessels between different vessel holdingpositions of the at least one static vessel holder.
 16. The systemaccording to claim 9, wherein the at least one static vessel holdercomprises at least one detection position and, after addition of thesecond reagent type, the controller is further programmed to control thevessel workstation for transferring the vessel held by the gripper tothe at least one detection position.
 17. The system according to claim15, wherein the vessel workstation comprises a shaking mechanism forshaking the vessel held by the gripper at least in part during transferof the vessel between different positions of the static vessel holder.